Differential roles of GluN2B in two types of chemical‐induced LTP‐mediated phosphorylation regulation of GluA1 at serine 845 in hippocampal slices

Abstract

Synaptic plasticity, such as long‐term potentiation (LTP) and long‐term depression (LTD), underlies the cellular mechanism of learning and memory. Chemical‐induced LTP, which facilitates biochemical analysis of molecular changes in brain slices or neuronal cultures, was accepted as an in vitro model for exploring synaptic plasticity. Chemical‐induced LTP, either by forskolin and rolipram or by glycine, is thought to be dependent on NMDA receptor. However, subunit specific dependence and regulation of NMDA receptor in chemical‐induced LTP remain poorly understood so far. In the present study, we found that phosphorylation of tyrosine 1472 at GluN2B was modulated by forskolin and rolipram‐induced LTP but not glycine‐induced LTP in hippocampal slices. Furthermore, elevated phosphorylation level of serine 845 at GluA1 by forskolin and rolipram‐induced LTP rather than glycine‐induced LTP was dependent on the activation of GluN2B, which is supported by the results from GluN2B antagonists, small interfering peptide and CRISPR‐Cas9‐mediated knock out of GluN2B. Taken together, we reveal a significant role of GluN2B in forskolin and rolipram‐induced LTP, uncovering NMDA receptor subunit specific dependence in a specified chemical‐induced LTP.Support or Funding InformationThis work was supported by National Natural Science Foundation of China Grant 31700882 (to Z.B.) and 31600863 (to W. L.), the start‐up fund of Hainan Medical University (to W. L.), the Tri‐Five Cultivating Project from Hangzhou Normal University 2017XJSGWXM209 (to Z.B.).